The prevalence of obesity is growing at an unprecedented rate in countries around the world, leading to increased morbidity and economic cost. Obesity is a consequence of a long-term positive imbalance in energy intake and expenditure leading to excessive deposits of adipose tissue. Food intake is controlled by a number of within-meal satiation signals. Cholecystokinin and serotonin are two such anorectic signals that have been shown to both independently mediate meal size, as well as interact in overall satiation. The mechanisms by which 5-HT and CCK combine to enhance suppression of food intake are not completely known but recent evidence suggests that these two anorectic signals interact at 5-HT3 and CCK-A receptors; which have been shown to be involved in energy balance. In addition, 5-HT3 receptors have been shown to mediate CCK-induced satiation possibly through mechanisms involving gastric feedback; however this has yet to be investigated. The goals of this proposal are to identify the gastric involvement in 5-HT3 receptor mediation of CCK-induced satiation, as well as examine the effects on daily food intake and body weight in response to chronic elevation of circulating 5-HT and CCK. [unreadable] [unreadable]